We have shown that the velocity of shortening, total heat production and myofibrillar and myosin ATPase activities are altered in cardiac hypertrophy secondary to pressure overload and thyroxine administration. The aim of the proposed research is to examine the hypothesis that there is a structural change in myosin from hypertrophied myocardium as an underlying cause of altered muscle performance. We will investigate two models of cardiac hypertrophy in the rabbit: 1) binding of the pulmonary artery which is known to result in depressed cardiac myofibrillar and myosin ATPase activities; and 2) thyroxine treatment which leads to an elevated cardiac myofibrillar and myosin ATPase activities. We will investigate the hypothesis that the hypertrophic process causes a conformational change in the region of the reactive first class sulfhydryl (SH1) group of myosin heavy chains. The SH1 group of myosin from control and hypertrophied hearts will be labeled selectively with 14C-iodoacetamide (14C-IAA), the myosins digested enzymatically, and the charge, and amino acid composition of 14C-IAA peptides compared. We will also determine the phosphate content of myosin light chain 2 and troponin-I from normal and hypertrophied hearts. Experiments will also include an analysis of the influence of phosphorylation on the enzymatic activity of myosin from control and hypertrophied hearts. These studies will provide information regarding the changes which occur in myosin during the development of hypertrophy as well as the extent to which these changes might explain alterations known to occur in the function of hypertrophied myocardium.